Study of C-C chemokine receptor 2 alleles in sarcoidosis, with emphasis on family-based analysis.

Prevailing models of sarcoidosis pathogenesis involve the activation of alveolar macrophages, aggregation of CD4+ T lymphocytes, and their accumulation in epithelioid cell granulomas. Increasing evidence suggests that each of these steps is modified by the host genetic constitution. Consequently, candidate susceptibility genes have been selected based on their potential function under this model. The C-C chemokine receptor 2 (CCR2) is involved in Th1 immune activity by recruiting competent cells and possibly by balancing response. CCR2 gene variants have been shown to be associated with sarcoidosis or, more specifically, with Löfgren's syndrome, a distinct form of acute sarcoidosis. We have studied three CCR2 gene polymorphisms (c.190G>A, c.840C>T, and c.4385A>T) in an extended sample of 1,203 patients with sarcoidosis and their relatives. Case-control comparisons and family-based genetic analyses did not support previous findings of an association between CCR2 gene variability and the risk of sarcoidosis. However, they confirmed linkage disequilibrium and showed positive linkage results (p = 0.034) and therefore suggest a susceptibility gene in the surrounding chromosomal region.